Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferative epidermis accompanied with parakeratosis and lymphocytic infiltration of the dermis; psoriasis is mainly manifested by erythemas and scales, and has complex pathogenesis and long disease course; it is easy to relapse and difficult to cure, severely affects the quality of life of patients. As compared with United States and Europe, the prevalence of psoriasis is lower but the absolute number of patients is greater and is increasing year by year in China. The objective of psoriasis treatment is to control the disease, delay the process of systematic development, alleviate symptoms such as erythemas, scales, topical thickening patches and the like, stabilize the disease condition, prevent recurrence, avoid side effects and improve the quality of life of patients and such treatment should follow regular, safe and individualized treatment principles. Currently, the therapeutic methods for psoriasis are mainly external drugs therapies and physical therapies. The external drugs include emollients, keratoplastics, keatolytics, corticosteroids, tretinoins, vitamin D3 derivatives, anthralin, tars, cytotoxic drugs and the like. The first-line drugs for topical treatment include tazarotene, corticosteroids with medium to strong effects, and calcipotriene. Physical therapies include long-wave ultraviolet (UVA) therapy, broad-spectrum UVB therapy, narrow-spectrum UVB therapy and photochemotherapy (PUVA). For refractory psoriasis such as moderate to severe psoriasis, pustule psoriasis, it is often difficult for topical treatment to produce a better therapeutic effect, while it has been confirmed that phototherapies especially PUVA have relatively good efficacy. PUVA is a method combining UVA (UVB can also be used in a small number of cases) with oral or topical psoralen (8-MOP, 5-MOP). Large amount of UVA irradiation may cause skin erythemas, burning skin, blisters and the like; and long-term use of PUVA may cause skin aging, pigmentation and skin cancers, and increase the risk of cataracts. Broad-spectrum UVB also may cause erythemas, sunburn, and pigmentation, and long-term irradiation is possibly carcinogenic. Narrow-spectrum UVB has fewer side effects such as erythemas, pigmentation, DNA damage, carcinogenicity and the like, and it has the same effectiveness as the early-stage of PUVA, but the period of remission is not long.
Photodynamic therapy (PDT) appeared in the late 1970s of the last century as a new therapeutic technique and it refers to a method which changes the function or morphology of cells of organisms or biological molecules and even causes cell damage and necrosis to achieve therapeutic effects, under the involvement of a photosensitizer and the action of light. At the beginning, PDT was mainly directed against (vascular) hyperplasic diseases, and then became one of the most active research fields in the science of tumor prevention and treatment all over the world. Recently, more and more attention has been paid to the treatment of non-tumor diseases with PDT, and for example, the non-tumor disease is genital warts, psoriasis, nevus flammeus, rheumatoid arthritis, ocular fundus macular disease, restenosis after angioplasty and the like. Currently, the PDT treatment of psoriasis is still in the research stage. Although some photosensitizer-mediated PDTs show good therapeutic effects in pre-clinical and clinical trials and in the treatment of a few cases, there is a lack of multi-central and large-scale clinical promotion around the world and there is also a lack of photosensitizer drugs used for psoriasis that acts as the main indication. The mechanism underlying the treatment of psoriasis with PDT is not fully clear yet. Existing researches indicate that it may be related to the following mechanisms: {circle around (1)} PDT may reduce the secretion of cytokines involved in the inflammatory mechanism, and change the secretion pattern of cytokines of monocytes in patients with psoriasis; {circle around (2)} PDT may inhibit the proliferation of keratinocytes; and {circle around (3)} PDT may promote T cell apoptosis at skin lesions of patients with psoriasis, correct the changes in the classification of lymphocytes, especially of T lymphocytes, and regulate the immune function to some extent. As compared with PUVA, PDT uses laser as an irradiation light source, has fewer side effects for long-term application and higher safety. With the development of photosensitizers, photosensitizers used for PDT therapy of psoriasis may have a reduced toxicity as compared with early photosensitive drugs such as psoralen, on the basis of improved efficacy.
The effect of PDT largely depends on the properties of the photosensitizer, and the emergence, development and application of PDT generally get improved gradually with the development of photosensitizers. From 1900 when it was firstly found in Germany that the combination of light and a photosensitizer could produce the cytotoxic effect to April of 1993 when Ministry of Health of Canada firstly approved the clinical application of porfimer sodium all over the world, basic researches and clinical applications of PDT had gained wide attention. A photosensitizer or its metabolite is a chemical substance which may selectively gather on a target. An ideal photosensitizer should have the following characteristics: {circle around (1)} it has a single component, clear structure and stable property; {circle around (2)} it has relatively strong phototoxicity to the target cells, strong efficacy, relatively low dark toxicity and fewer side effects; {circle around (3)} it has a relatively long retention time in target tissues, but does not remain or accumulate in the body permanently; {circle around (4)} it has relatively high production of singlet oxygen and relatively long lifetime; {circle around (5)} it has strong absorption in phototherapy window (600 nm˜900 nm) so as to facilitate the use of a light source which may penetrate the human tissues more deeply in the treatment; and {circle around (6)} it is soluble at physiological pH value. According to the structures and components of the photosensitizers, they may be classified into porphyrins, chlorophylls, dyes, Chinese herbal medicines and the like; according to the development time and the properties, photosensitizers may be classified into the first-, second- and third-generation photosensitizers. The first-generation photosensitizers appeared between the 1970s and the early 1980s; the main photosensitizer was a hematoporphyrin derivative (HpD); most photosensitizers were complex porphyrin mixtures with indefinite composition; their structures were controversial; they had poor absorption for red lights and poor capability of penetrating tissues; the time intervals between administration and irradiation was long; they were slowly excreted and the time for avoiding light after administration was long. Due to the above disadvantages of the first-generation photosensitizers, researches on the second-generation photosensitizers begun in the late 1980s. Improvements on the structure of porphyrin derivatives and isolation of monomer components such as benzoporphyrin derivatives (BPD), hematoporphyrin monomethyl ether (HMME) and the like were conducted firstly. Other substances studied mostly were monohydroporphines, phthalocyanines and derivatives of chlorophyll a degradation products. Phthalocyanines, coordination complexes of porphyrins, are big conjugated systems formed by 4 pyrrole units linked together via 4 N atoms. The big phthalocyanine ring can react with a metal element via complexation and may be substituted with various substituents. Phthalocyanine photosensitizers have an absorption wavelength of 600 nm to 800 nm and possess the following advantages: relatively high purity, relatively good light and heat stability as well as physiological activity, relatively strong absorption for the red light region, relatively good amphipathicity (hydrophobicity and hydrophilicity), low dark toxicity, good selectivity to tumors, relatively high molar extinction coefficients and the like. As compared with the first-generation photosensitizers, the second-generation photosensitizers have a single component, definite molecular structures, higher singlet oxygen quantum yields, fewer side effects and faster excretion in the body. Researches on the third-generation photosensitizers that are developed in recent years aim to further improve the efficacy and to reduce side effects, and attentions are paid to the applications of photosensitizers in diagnosis, dose monitoring, efficacy assessment and other aspects. As for the improvement of efficacy and reduction of side effects, the main strategy is the cross-linking with some special chemical substances on the basis of the second-generation of photosensitizers, thereby achieving the synergistic treatment by improving the selectivity for the target tissue or imparting new efficacy to the photosensitizers.
α-(8-quinolinyloxy) mono-substituted phthalocyanine zinc is a metal phthalocyanine complex, in which two structures, phthalocyanine and quinoline, are fused together, making the complex have the structural characteristics of both metal phthalocyanine and quinoline. The complex has characteristics such as definite structure and easy separation. The complex has an absorption wavelength of about 670 nm, a relatively high yield of fluorescence quantum and high oxidation stability; and the complex may be prepared into stable aqueous solution for use. Previous pharmacodynamics studies have confirmed the strong anti-tumor activity of the complex.